Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis

PLoS One. 2013;8(3):e57963. doi: 10.1371/journal.pone.0057963. Epub 2013 Mar 1.

Abstract

Background: A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis.

Methods: Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy.

Results: The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy.

Conclusions: The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and thus comprises a significant step towards personalized pain medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Electric Stimulation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain / complications
  • Pain / drug therapy*
  • Pain / physiopathology
  • Pain Measurement / methods
  • Pain Threshold / drug effects
  • Pain Threshold / physiology*
  • Pain Threshold / psychology
  • Pancreatitis, Chronic / complications
  • Pancreatitis, Chronic / drug therapy*
  • Pancreatitis, Chronic / physiopathology
  • Placebos
  • Precision Medicine
  • Pregabalin
  • Pressure
  • Sensitivity and Specificity
  • Support Vector Machine
  • Treatment Outcome
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Analgesics
  • Placebos
  • Pregabalin
  • gamma-Aminobutyric Acid

Grants and funding

This research was supported by a free grant from Pfizer Research and Development and the Danish Agency for Science, Technology and Innovation: Det Strategiske Forskningsråd; grant No.10-092786. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.